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Background: Endoscopy has been regarded as an effective modality for draining pancreatic collections, pseudocysts, and abscesses. This study analyzes our experience with endoscopic transmural drainage of pancreatic pseudocysts and compares the outcomes in patients with postsurgical and pancreatitis-associated ones. Methods: Patients who underwent endoscopic drainage of a pancreatic pseudocyst from January 1999 through June 2008 were included in this retrospective analysis. The specific indication for attempting the procedure was the presence of direct contact between the pseudocyst and the gastric wall. All the drainages were carried out via a transgastric approach, and one or two straight plastic stents (10 or 11.5 French) were positioned. A comparative analysis of short- and long-term results was made between patients with postoperative pseudocysts (group A) and patients with pancreatitis-associated pseudocysts (group B). Results: Fifty-five patients were included in the study, 25 in group A and 30 in group B. Overall, a single stent was inserted in 84.0% of patients, while two stents were needed in the remaining 16.0%. The technical success rate was 78.2%, whereas procedure-related complications were 16.4%. Complications included pseudocyst superinfection and major bleeding and were managed mainly by surgery. Mortality rate was 1.8% (1 patient). There were no significant differences in the technical success rate and procedure-related complications between the two groups ( p = 0.532 and 0.159, respectively) Recurrences were 13.9% and significantly more common in group B ( p = 0.021). In such cases, a second endoscopic drainage was successfully performed. Conclusion: Transmural endoscopic treatment of pancreatic pseudocysts is feasible and has a technical success rate of 78.2%, without differences related to the pseudocyst etiology. Recurrences, on the other hand, are more common in patients with pancreatitis. Given the severe complications that may occur after the procedure, we recommend that endoscopic drainage be performed in a tertiary-care center with specific expertise in pancreatic surgery. [ABSTRACT FROM AUTHOR]